Enfermedades Inflamatorias y Degenerativas
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Integrantes
Integrantes
Investigadoras Principales:
María Luisa Nieto
Marita Hernández
Investigadores Predoctorales:
Hugo Calvo
Mónica Macías
Técnico de Laboratorio:
Mabel Cabero
Breve descripción del grupo
Our laboratory is interested in the signal transduction mechanisms regulating inflammatory and degenerative processes in cells of cardiovascular relevance. Our work focuses on the involvement of certain proinflammatory proteins such as tumor necrosis factor a (TNFa) or secreted phospholipase A2 (sPLA2) in the development of atherosclerotic lesions. Our system model is the THP-1 monocytic cell line, in which we have described that both TNFa and sPLA2 are able to induce different actions, ranging from gene expression, cell differentiation, migration and apoptosis. Analyses of the signaling cascades triggered by these proteins include small molecular weight GTPase activation, MAPK activation, and PKB/Akt involvement. The correct definition of the steps implicated in generating biochemical signals will eventually allow us to assay different drugs. We have already initiated studies with the anti-lipidemic drugs statins and 2-hydroxy-3-methyl-glutaryl-CoA inhibitors. We are also interested in defining the molecular basis of a process called astrogliosis, which occurs when astrocytes proliferate and change their shape in response to external aggression. These cells also release a variety of factors such as adhesion molecules, cytokines, and growth factors. These events may be of special relevance during ischemia. We work with glial cells and stimulate them with different agonists (thrombin, TNFa, sPLA2, lysophosphatidic acid). We are also interested in the possible interactions between these ligands at the level of receptor transactivation, cooperative signaling or desensitization.
Hitos más relevantes
R.Martin, C.Cordova, B.Gutiérrez, M.Hernández, M.L. Nieto (2017) A dangerous liaison: Leptin and sPLA2-IIA join forces to induce proliferation and migration of astrocytoma cells. PloS One. 12 (3):e0170675
L. Caltana,M.L. Nieto, A. Brusco (2015) Oleanolic acid: a promising neuroprotective agent for cerebral ischemia. Neural Regeneration Research. 10: 540-1
Torres A, Cachofeiro V, Millán J, Lahera V, Nieto M.L, Martín R, Bello E, Alvarez-Sala L.A. (2015) Red wine intake but not other alcoholic beverages increases total antioxidant capacity and improves pro-inflammatory profile after an oral fat diet in healthy volunteers. Revista Clínica Española. 215:486-94
B.A. Caltana L., L. Rutolo D., Nieto M.L. (2014) Further evidence for the neuroprotective role of oleanolic acid in a model of focal brain hypoxia in rats. Neurochem Int. 79:79-87
R. Martin, C. Cordova, J.A. San Román, B. Gutiérrez, V. Cachofeiro, M.L. Nieto (2014) Oleanolic acid modulates the inmmune-inflammatory response in mice with experimental autoimmune myocarditis and protects from cardiac injury. Therapeutic implications for the human disease. Journal of Molecular and Cellular Cardiology. 72: 250-262
C.Cordova, B. Gutiérrez, C. Martínez-García, R. Martin, P. Gallego-Muñoz,...M.L. Nieto (2014) Oleanolic acid controls allergic and inflammatory responses in experimental allergic conjunctivitis. PloS One. 9(4): e91282
R. Martin, M. Miana, R. Jurado-López, J.C. Muñoz,...M.L. Nieto (2012) DIOL triterpenes block profibrotic effects of angiotensin II and protect from cardiac hypertrophy. PloS One. 7(7): e41545
Martin R, Hernández M, Córdova C,Nieto M.L, (2012) Natural triterpenes modulate immuneinflammatory markers of experimental autoimmune encephalomyelitis: therapeutic implications for multiple sclerosis. Br J Pharmacol. 166:1708-23
R. Martin, C. Cordova,M.L. Nieto (2012). Secreted phospholipase A 2-IIA-induced a phenotype of activated microglia in BV-2 cells requires epidermal grow facor receptor transactivation and proHB-EGF shedding. Journal of Neuroinflammation. 9(1): 154
R. Martin, J. Carvalho-Tavares, M. Hernández, M. Ames, V. Ruiz-Gutiérrez,M.L. Nieto (2010) Beneficial actions of oleanolic acid in an experimental model of multiple sclerosis: a potential therapeutic role. Biochemical pharmacology. 79(2): 198-208
Proyectos destacados
Título del proyecto: Identificación de nuevas dianas y estrategias terapéuticas en Miocarditis: Factores lipídicos y proteicos que afectan a la mitocondria y al estrés oxidativo; del modelo animal (PID2022-139513OB-I00).
Duración: 2023 – 2026.
Entidad financiadora: Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación y FEDER, UE.
Presupuesto: 143.750 €.
Investigador Principal: María Luisa Nieto Callejo.
Proyecto PID2022-139513OB-I00 financiado por:
Programa Estatal de Fomento de la I+D+I orientada a los Retos de la Sociedad:
Retos Investigación 2016: SAF2016-81063-"Nuevos mediadores de la inflamación relevantes en las alteraciones del miocardio. Potencial terapéutico de compuestos bioactivos".
Retos-Colaboración 2016: RTC-2016-4852-2-"Obtención de Nutracéuticos e ingredientes funcionales derivados de aceitunas para frenar procesos degenerativos asociados con el envejecimiento. NUDACE
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